Study Assessing PTI-428 Safety, Tolerability, Pharmacokinetics and Effect in Subjects With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect of PTI-428 in Subjects With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03591094
• Other study ID #: PTI-428-06
• Status: Completed
• Phase: Phase 2
• Start date: August 21, 2018
• Est. completion date: February 18, 2019

Study information

• Verified date: February 2020
• Source: Proteostasis Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study population is comprised of adult subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation and are currently receiving background treatment with tezacaftor/ivacaftor for a minimum of 1 month prior to Day 1. The planned sample size is approximately 40 subjects. 20 subjects will be assigned to PTI-428 dose level 1 or placebo and 20 subjects will be assigned to PTI-428 dose level 2 or placebo. At each dose level, subjects will be randomized at a 3:1 randomization ratio. Subjects will receive once daily oral doses of PTI-428 or placebo for 28 days, while the subjects continue to receive background treatment with tezacaftor/ivacaftor per product label. The study drug administration period will be followed by a 14-day safety follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 18, 2019
• Est. primary completion date: February 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of CF with the F508del/F508del genotype on record

• On tezacaftor/ivacaftor dosing for both label indication and per label dosing for a minimum of 1 month on Day 1

• Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive

• Clinically stable with no significant changes in health status within 14 days of Day 1

• Non-smoker and non-tobacco user for a minimum of 28 days prior to screening and for the duration of the study

Exclusion Criteria:

• Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1

• History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)

• History of organ transplantation

• Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 14 days of Day 1

• Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1

• History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator

• Pregnant or nursing women

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• PTI-428
Active
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Central Florida Pulmonary Group	Altamonte Springs	Florida
United States	Michigan Medicine, University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	National Jewish Health	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Iowa, Roy J and Lucille A Carver College of Medicine	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Universitey of Louisville, Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky
United States	Dartmouth Hitchcock Medical Center	Manchester	New Hampshire
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center	Peoria	Illinois
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	University of Utah	Salt Lake City	Utah
United States	Stanford University	Stanford	California
United States	University of Arizona	Tucson	Arizona
United States	The University of Texas Health Science Center at Tyler - Center for Clinical Research	Tyler	Texas
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Proteostasis Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in nasal epithelial CFTR mRNA and protein expression over time		Baseline through Day 42
Other	Change in CFQ-R over time		Baseline through Day 42
Other	Cmax of PTI-428 metabolites, if applicable		28 days
Other	Tmax of PTI-428 metabolites, if applicable		28 days
Other	AUC0-t of PTI-428 metabolites, if applicable		28 days
Primary	Number of subjects with treatment-emergent adverse events (TEAEs)	Safety and tolerability will be assessed by adverse events (AEs), safety labs, electrocardiograms (ECGs), physical examinations and vital signs.	Baseline through Day 42
Secondary	Maximum plasma concentration (Cmax)		28 days
Secondary	Time of Cmax (Tmax)		28 days
Secondary	Area under the concentration time curve from time 0 to time of last measurable concentration (AUC0-t)		28 days
Secondary	Change in FEV1 over time		Baseline through Day 42
Secondary	Change in sweat chloride over time		Baseline through Day 42

External Links

•   Information about the sponsor